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Detecting Alzheimer's 20 years before symptoms occur

Ten of the 14 members of the Reisweig family have developed dominantly inherited… (Gary Reisweig )

Some signs of Alzheimer's disease appear in cerebrospinal fluid 10 or 20 years before symptoms of the disease appear in families with an inherited form of the disease, a finding that may help provide early diagnosis in those with sporadic forms of the disease, researchers said Wednesday. The findings may also provide a group of subjects in whom potential Alzheimer's drugs can be tested to determine if they work better when used at the earliest stages of the disease, according to researchers from the Washington University School of Medicine in St. Louis.

Dr. Randall Bateman of Washington University is a director of the Dominantly Inherited Alzheimer's Network (DIAN), a collaboration of researchers who are studying the form of Alzheimer's called dominantly inherited Alzheimer's. As the name implies, patients with a certain mutated gene will always inherit Alzheimer's, with symptoms beginning in the 50s, 40s or even sometimes the 30s. The researchers can thus study families in which parents pass the gene on to their offspring to look for very early signs of the disease. The disorder is very rare, however, accounting for only about 1% of Alzheimer's cases, so researchers at many institutions in the DIAN group must pool their resources. The researchers have now enrolled 184 family members, including some with the mutation and others without it. They hope eventually to enroll 400.

Scientists know that patients with Alzheimer's disease have above-normal amounts of tau protein in their cerebrospinal fluid (CSF) and below-normal levels of a precursor of beta-amyloid. Those proteins are responsible for forming the plaques and tangles in the brain that are characteristic of Alzheimer's.

Among other things the team has been studying, the DIAN researchers examined levels of the two proteins in CSF in siblings with the mutation and those without it. Bateman reported Wednesday at a Paris meeting of the International Conference on Alzheimer's Disease that, at times up to 30 years before the expected onset of symptoms, children with the mutated gene have unusually high levels of beta-amyloid and lower-than-normal levels of tau protein. About 10 years before symptoms develop, those situations reverse, and CSF levels of the proteins become more characteristic of patients with Alzheimer's.

The team is now making plans to test new drugs in the family members. There are, effectively, no drugs that have proved useful in slowing the progression of Alzheimer's. Some scientists believe that is because the disease has progressed so far when treatment is begun that the drugs have no value. If patients could be treated at an earlier stage, the drugs might work better. The team already has 11 candidates that might undergo testing.

A variety of research suggests that the dominantly inherited form of Alzheimer's follows much the same course as the far-more-common forms of the disease. Researchers thus hope that any clues they obtain from the DIAN group will be applicable to all patients.